Each of the applications, patents, and papers cited in this application and in as well as each document or reference cited in each of the applications, patents, and papers (including during the prosecution of each issued patent; “application cited documents”), and each of the PCT and foreign applications or patents corresponding to and/or claiming priority from any of these applications and patents, and each of the documents cited or referenced in each of the application cited documents, are hereby expressly incorporated herein.
The cornea is the transparent structure that forms the anterior one sixth of the outer coat of the eye and is responsible for more than two thirds of its refractive power. The cornea consists of several layers, including the epithelium, stroma, and single-celled endothelium. The endothelium is the most posterior layer, interfacing with the aqueous humor of the anterior chamber of the eye. Corneal clarity is dependent on a relatively dehydrated state. The endothelium plays a key role in maintaining dehydration by both preventing aqueous humor from entering the cornea and by pumping fluid from the corneal stroma into the anterior chamber. Corneal endothelial cells do not replicate. When destroyed by disease or surgery, the remaining cells enlarge and spread out to cover the posterior corneal surface, thus decreasing the cell density (cell count). Corneas with extremely low endothelial cell densities can no longer maintain a dehydrated state. The corneas may decompensate, swell, and become cloudy over time, with an associated loss of visual acuity.
Cornea transplants are used to improve visual acuity by replacing the opaque or distorted host tissue by clear healthy donor tissue. The most common indication in this category is pseudophakic bullous keratopathy, followed by keratoconus, corneal degeneration, keratoglobus and dystrophy, as well as scarring due to keratitis and trauma. Donor corneas provide the source material for the transplants. Since the health of the cornea at the time of surgery has an impact upon outcomes, it is critical that the cornea container used to store the cornea from the time that it is harvested from the donor eye globe to the point at which it is used in surgery maintains the cornea in an optimal state of health. This need has become even more imperative as LASIK surgery, which renders donor corneas unsuitable for transplant, has become widely accepted in society. Thus, there is a shrinking source of donor corneas and less opportunity to be selective among donated corneas, putting even more importance on the capability of the cornea container to maintain optimal cornea health.
Once removed from the donor, corneas are placed in a cornea container, which is filled with preservation medium and delivered to an eye bank. The eye bank stores the cornea, performs quality assessments by way of slit lamp and specular microscopy, and delivers the cornea to a surgical location. The cornea container should allow the technician that harvests the cornea to easily deposit the cornea into the container, facilitate quality assessments, and make it easy for those performing surgery to easily remove the cornea from the storage container. Unfortunately, cornea containers that are used, or have been conceived, are suboptimal.
The earliest storage containers merely placed the cornea in a vial filled with preservation medium. However, there was no control over the position of the cornea, causing problems that included trapping the endothelium in a position that cut it off from the surrounding medium, allowing the epithelium to make contact with the walls of the vial, letting gas bubbles contact the cornea, and preventing lack of controlled positioning for specular microscopy and slit lamp evaluation. Although it was easy to deposit the cornea into the vial, the ability to easily retrieve the cornea was difficult.
The vial container was improved by attaching the cornea to the lid with a suture in order to allow easier removal of the cornea. But attaching the cornea to the suture required more handling of the cornea by those retrieving them from the donor. It still allowed the endothelium to become trapped in a position that cut it off from the surrounding medium, allowed the epithelium to make contact with the walls of the vial, let gas bubbles contact the cornea, and prevented lack of controlled positioning for specular microscopy and slit lamp evaluation.
In an attempt to overcome some of the problems of attaching a cornea to a suture, U.S. Pat. No. 4,695,536 describes a cornea container that retains the cornea in a fixed position within a medium vial. A steel wire is attached to the lid. An alligator clip is attached to the opposite end of the wire. The person retrieving the cornea attaches the sclera (the tough white opaque tissue that surrounds the cornea) to the alligator clip and carefully attaches the lid so the epithelium comes to reside upon a plurality of dividers that reside in the body of the cornea container. Although this configuration resolves some of the positioning problems of the suture approach, such as preventing the endothelium from being cut off from its media supply, the epithelium is forced to be in direct contact with the dividers that reside in the vial. Direct physical contact between the dividers and the epithelium can cutoff media access, affecting the health of the cells that comprise the epithelium, and can physically damage the epithelium as it is dragged across the dividers when the cornea is removed for surgical implantation. Also, the technician is required to transfer the cornea from forceps to the retaining clip in a manner that prevents damage to the cornea. That process can add contaminants to the container as the technician is likely to place their gloved hands directly upon the alligator clip to open it during the process rather than find a clever way to actuate the alligator clip with a sterile tool. Touching a component that resides within the container, even with gloves, is not good practice because bioburden level is dependent on what the technician's gloves have contacted previously and is also impacted by the skill level of the technician. Thus, the process of using this storage container increases contamination risk and is highly dependent on the skill and patience of the technician. Manipulation of the tissue by the technician may also damage the non-regenerating endothelium. Also, there is no geometry to prevent gas from contacting the cornea as the container is shipped, subjecting the cornea to potential damage in transit.
U.S. Pat. No. 4,844,242 also attempts to prevent the cornea endothelium from becoming trapped face down in a medium vial by orienting the cornea in a fixed position within the retaining lugs of a support ring. However, the harvesting process currently used to obtain donated corneas often leads to corneas of various diameters and rarely results in a completely circular excision. The apparatus '242 does not easily accommodate corneas of various diameters, or those that are not circular, since the support ring and the retaining lugs only allow about a 12% variation in cornea diameter before extra trimming is required. The more the cornea is handled for trimming, the more potential problems arise. For example, twisting, stretching, additional contact with forceps, and extra cutting increase the chances of damage to the tissue, particularly at its edges and on the endothelial cell surface. Furthermore, the outcome can vary from technician to technician since cutting the corneas to match the limited diameters accepted by the apparatus of '242 requires patience, time, and a high level of skill. In general, those obtaining donor corneas desire the least amount of preparation and exposure to the environment necessary before the cornea is placed into its medium storage container. Moreover, the act of using forceps to press the cornea into the retaining lugs of the support ring can inflict further damage to the cornea. Still another problem with the apparatus of '242 is that gas in the container has the potential to make contact with the cornea during shipping, and can even become trapped in direct contact with the endothelium depending on the orientation of the container.
For the reasons described, the US market has avoided the use of the free floating vial, and rejected sutured lids attached to a vial, as well as devices described in patents '536 and '242. Instead, the US standard is a cornea container that allows gravity to position the cornea in a basket that holds the cornea in a fixed location within the container. Throughout, we refer to the cornea container which has come to be the industry standard as a “conventional container”. The conventional cornea container includes a corneal basket to hold the cornea. It has completely dominated the US market since at least the late 1980's. The conventional container achieves its popularity because it is so easy to place the cornea into the container's corneal basket and remove it from the container's corneal basket with forceps. Just placing the lid on the container automatically fixes the position of the cornea, the cornea is positioned for examination by slit lamp and specular microscopy, and the process is not highly dependent on the skill level of the technician.
In use, a technician merely drops the cornea, epithelial side down, into the medium filled container. The cornea gravitates to reside upon a corneal basket, formed of a group of prongs emanating from the base of the container that are arranged in a circular pattern. The corneoscleral disc resides upon the prongs in a position such that the plane in which the sclera resides in is generally parallel to the top and the bottom of the container. This allows examination of the cornea by slit lamp and/or specular microscopy. The lid is designed so that a portion of it functions as a viewing window. No matter the orientation of the container, the cornea is kept from falling out of the basket by the viewing window, which is typically only about 0.05 inches from the sclera. A relieved area in the lid acts as a gas trap and occupies the perimeter of the viewing window, controlling the location of gas within the container. A similar gas trap is present in the container. The cornea basket is positioned away from the container walls, allowing gas to move from the lid to the bottom of the container without contacting the corneoscleral disc as the conventional container is inverted.
The conventional cornea container was introduced by Coopervision Inc, Irvine Calif. The basket included eight prongs that rose from the bottom of the container. The corneoscleral disc resided in contact with the prongs. The container left room for improvement however. The basket design included prongs which obstructed the ability for slit lamp observation of the epithelium. Around the late 1980's, Bausch & Lomb entered the market with a conventional cornea container that allowed slit lamp observation. Their product is called the Independent Corneal Viewing Chamber™, and it came to dominate the US market.
Although the conventional cornea container has many advantages over any other proposed or previously tried cornea container, we have discovered that the design acts to limit cornea health. One problem, detailed within, is that the design of the corneal basket impedes the effective use of preservation medium within the container and as a result is suboptimal for maintaining corneal health. The other problem is that the lid design allows the sclera to become suctioned to it, thereby cutting off solute movement to the endothelium, and in some cases, even trapping gas against the endothelium.
A review of conventional container basket geometry helps clarify the problem of effective use of preservation medium within the container. When the cornea resides in the Coopervision cornea container, the prongs only provide a small open area between medium residing within the corneal basket and that outside of the corneal basket. The cross-sectional area of open space (about 0.69 in2) for medium communication is exceeded by that of cross-sectional space occupied by prongs. There is only about 38% of the corneal basket open for preservation medium communication. The distance between prongs is also limited to about 0.1 inch, which acts to trap gas that may form during medium temperature increases as will be explained later. An additional problem exists with the width of the prongs, as measured from the inner diameter to the outer diameter of their basket arrangement. The width of the corneoscleral disc support section is virtually maintained constant from the base of the prong to the point of disc contact (i.e. along the height). That adds further resistance to medium communication. For example, the Coopervision prongs have a width of about 0.4 inches.
The same problems exist in Bausch & Lomb's Independent Corneal Viewing Chamber™, which will be detailed further within.